Apparatus and method of assessing a narrowing in a fluid filled tube

ABSTRACT

An apparatus and method of assessing a narrowing in a fluid filled tube having a fluid flow pressure wave having a backward-originating pressure component and a forward-originating pressure component without taking a flow velocity measurement, comprising: taking pressure measurements in the tube; separating the pressure components into the backward-originating pressure component and the forward-originating pressure component; identifying a time window when the differential of flow velocity (dU) is minimal or absent; and deriving the backward and forward pressure components for pressure measurements taken in at least the time window.

CROSS-REFERENCE TO RELATED APPLICATION

This application is a continuation of U.S. application Ser. No.13/345,495 filed Jan. 6, 2012, now U.S. Pat. No. 9,026,384, which claimspriority to United Kingdom Patent Application No. GB1100137.7, filedJan. 6, 2011, the disclosures of which are hereby incorporated byreference in their entirety.

FIELD OF THE INVENTION

This invention relates to an apparatus and method of assessing anarrowing in a fluid filled tube.

BACKGROUND TO THE INVENTION

A fluid filled tube or vessel formed with a constriction or narrowingcan be analysed to measure the magnitude of the constriction ornarrowing.

An example of a fluid filled tube or vessel formed with a constrictionor narrowing is a blood vessel having a stenosis. Assessment ormeasurement of the constriction can result in a useful parameter togauge the extent of the constriction.

A standard methodology for assessment of a constriction in a fluidfilled tube such as a coronary stenosis is fractional flow reserve(FFR). This technique measures the drop in pressure at two points alonga vessel; see FIG. 1 of the accompanying drawings, under conditions ofmaximal achievable hyperaemia in a coronary environment. The Pdmeasurement comes from a pressure sensor on the wire and the Pameasurement comes from the catheter. A comparison is then made byexpressing the mean distal pressure (Pd), as a proportion of meanproximal pressure (Pa), wherein the values are mean Pa and Pd over theentire cardiac cycle, taken over at least one complete cardiac cycle(but usually an average of 3 or more beats):

${{Fractional}\mspace{14mu} {Flow}\mspace{14mu} {Reserve}\mspace{14mu} ({FFR})} = \frac{P_{d}}{P_{a}}$

Conditions of maximal hyperaemia are usually only achievable byadministration of potent vasodilators such as adenosine or dipyridamole.Such vasodilators are necessary to minimise resistance from the distalvascular bed to accurately estimate the drop in pressure across astenosis. It would be preferable not to have to use vasodilators.

Distal pressure arises from resistance of the microcirculation, inaddition to active compression of small microcirculatory vessels whichpermeate the myocardium. When flow is measured simultaneously atdifferent sites, it is possible to separate the pressure componentsarising from the distal myocardium (backward-originating pressure), fromthose arising from the proximal end (forward-originating pressure),

${dP}_{+} = \frac{1}{2\left( {{dP} + {\rho \; c\; {dU}}} \right)}$${dP}_{-} = \frac{1}{2\left( {{dP} + {\rho \; c\; {dU}}} \right)}$

where dP is the differential of pressure, p=density of blood, c=wavespeed, and dU is the differential of flow velocity.

P₊ isolates forward originating pressure by removing thebackward-originating component, and therefore negates the need foradministration of vasoactive agents such as adenosine. Thus by comparingthe ratio of P₊ on either side of a stenosis it is possible to estimatestenosis severity without requiring maximal hyperaemia to be achieved.The isolated forward pressure ratio is expressed as:

${{Forward}\mspace{14mu} {pressure}\mspace{14mu} {ratio}} = \frac{P_{+ {distal}}}{P_{+ {proximal}}}$

Whilst the forward pressure ratio offers a considerable step forward asadministration of vasodilator compounds are not required, it requiresflow velocity to be measured in addition to pressure. This requiresconsiderable extra skill, additional hardware and added expense.

It is an object of the invention to provide an apparatus and method ofassessing a narrowing in a fluid filled tube which does not require ameasurement of flow velocity, fluid flow rate, in addition to pressuremeasurement.

One aspect of the present invention provides a method of assessing anarrowing in a fluid filled tube having a fluid flow pressure wavehaving a backward-originating pressure component and aforward-originating pressure component without taking a flow velocitymeasurement, comprising: taking pressure measurements in the tube;separating the pressure components into the backward-originatingpressure component and the forward-originating pressure component;identifying a time window when the differential of flow velocity (dU) isminimal or absent; and deriving the backward and forward pressurecomponents for pressure measurements taken in at least the time window.

Another aspect of the present invention provides an apparatus to assessa narrowing in a fluid filled tube having a fluid flow pressure wavehaving a backward-originating pressure component and aforward-originating pressure component without taking a flow velocitymeasurement, the apparatus comprising: a pressure measurement deviceoperable to take pressure measurements in the tube; and a processoroperable to separate the pressure components into thebackward-originating pressure component and the forward-originatingpressure component; identify a time window when the differential of flowvelocity (dU) is minimal or absent; and to derive the backward andforward pressure components for pressure measurements taken in at leastthe time window.

A further aspect of the present invention provides a processorconfigured to assess a narrowing in a fluid filled tube having a fluidflow pressure wave having a backward-originating pressure component anda forward-originating pressure component without taking a flow velocitymeasurement, the processor: analysing pressure measurements taken in atube; separating the pressure components into the backward-originatingpressure component and the forward-originating pressure component;identifying a time window when the differential of flow velocity (dU) isminimal or absent; and deriving the backward and forward pressurecomponents for pressure measurements taken in at least the time window.

A yet further aspect of the present invention provides a data storagemedium carrying a computer program to assess a narrowing in a fluidfilled tube having a fluid flow pressure wave having abackward-originating pressure component and a forward-originatingpressure component without taking a flow velocity measurement, theprogram: analysing pressure measurements taken in a tube; separating thepressure components into the backward-originating pressure component andthe forward-originating pressure component; identifying a time windowwhen the differential of flow velocity (dU) is minimal or absent; andderiving the backward and forward pressure components for pressuremeasurements taken in at least the time window.

BRIEF DESCRIPTION OF THE DRAWINGS

In order that the present invention may be more readily understood,embodiments of the invention will now be described with reference to theaccompanying drawings, in which:

FIG. 1 is a schematic diagram of a tube formed with a constriction withproximal (Pa) and distal (Pd) pressure measurement sites;

FIG. 2 is a schematic not-to-scale diagram of an apparatus embodying thepresent invention;

FIG. 3 is a flow diagram illustrating a method embodying the presentinvention;

FIG. 4 shows an example of a free wave period in a cardiac environment,which free wave period is used in an apparatus and method embodying thepresent invention.

DESCRIPTION

This invention provides an apparatus and method of assessing a narrowingin a fluid filled tube by measuring the pressure in the tube and doesnot require a measurement of flow velocity, fluid flow rate, in additionto the pressure measurement.

In a fluid flow system, the separated pressures are given as

${dP}_{+} = \frac{1}{2\left( {{dP} + {\rho \; c\; {dU}}} \right)}$${dP}_{-} = \frac{1}{2\left( {{dP} - {\rho \; c\; {dU}}} \right)}$

where dP is the differential of pressure, p=density of blood, c=wavespeed, and dU is the differential of flow velocity. The isolatedpressure ratio, comparing the ratio of P₊ or P⁻ on either side of aconstriction provides a measure, estimate or indication of the severityof the constriction.

The isolated forward pressure ratio using separated pressures is thus:

$\frac{P_{+ {distal}}}{P_{+ {proximal}}}$

Or isolated backward pressure ratio,

$\frac{P_{- {distal}}}{P_{- {proximal}}}$

Calculating the isolated pressure ratio using this technique gives apressure only assessment of the severity of the constriction.

Referring to FIG. 2, an apparatus 1 embodying the invention comprises aprobe 2 such as an intra-arterial pressure wire (WaveWire or Combowire(Volcano Corp.) or Radi pressure wire (St Jude Medical) with a pressuremeasurement transducer 3—i.e. a device measuring pressure (P), and aprocessor 4 to analyse and operate on the pressure measurements. Asignal line 5 relays the pressure measurement signal from the transducer3 to the processor 4. The signal line 5 is illustrated both as a wiredconnection 5 and as a wireless connection 5′—either configuration isavailable.

The processor 4 operates on the pressure measurements received from thetransducer 3 in accordance with a number of algorithms which arediscussed in greater detail below. The apparatus 1 may be provided inthe following configurations or combination of configurations, but theseare not an exhaustive list of configurations: a stand-alone deviceincorporating a probe with pressure measurement capacity in wiredconnection with a processor to provide on-device analysis;

-   -   i) a device incorporating a probe with pressure measurement        capacity in wireless connection with a processor to provide        analysis at the processor;    -   ii) a stand-alone device incorporating a probe with pressure        measurement capacity and a data storage device operable to        record measurement data for real time or subsequent        communication to a processor to provide analysis at the        processor (real time and/or off-line); and    -   iii) a device incorporating a probe with pressure measurement        capacity in wireless connection with a data storage device        operable to record measurement data for real time or subsequent        communication to a processor to provide analysis at the        processor (real time and/or off-line).

In the cardiac environment where the apparatus 1 is configured as partof haemodynamic equipment, the apparatus is configured using theprocessor 4 in the haemodynamic equipment, such as in McKessonequipment—Horizon Cardiology™, a cardiovascular information system(CVIS). Such configurations are particularly effective for the equipmentprocessor to perform off-line analysis of the pressure data.

The apparatus 1 (and in particular the probe 2) can be used incombination with other haemodynamic equipment, medical imaging equipmentand/or in-patient marker location equipment.

In a cyclic fluid flow system, there are time windows in which the rateof change of the fluid flow velocity tends to zero—i.e. dUtends to zero.At these times, termed here “wave free periods”, it is possible toseparate the wave pressure in the fluid at a measurement site intoforward and backward pressures using the pressure waveform alone. Thisnegates the need for measurement of flow velocity.

In a specific example of a cardiac cycle, at any point in the cardiaccycle dP₊ is determined by dP+ρ c dU. dU is large during parts of thecardiac cycle when significant proportions of wave energy are present(i.e. during left ventricular contraction). However, there are times inthe cardiac cycle when dUtends to zero. This can be a single moment orsample in time, or a multiple moments or samples in time. At such times,the dUterm can be cancelled and dP₊ or dP⁻ estimated using the dP termalone.

In accordance with this example of the invention, pressure samples aretaken at or over the wave free period when dUtends to zero. Preciseadherence to pressure sampling at or over the wave free period is notessential but pressure sampling does need to take place when theinfluence of dU is minimised and preferably when tending to zero.

At or over the wave free period when the influence of dU is minimised ornegated entirely, the dU side is cancelled from the separated pressuresso:

dP₊ is calculated as

${dP}_{+} = \frac{1}{2\left( {{dP} + {\rho \; c\; {dU}}} \right)}$

and dP⁻ is calculated as

${dP}_{-} = \frac{1}{2\left( {{dP} - {\rho \; c\; {dU}}} \right)}$

With the dU term cancelled) the separated pressures are calculated as:

dP ₊=1/2dP

and

dP ⁻=1/2dP

When dU tends to zero, the dU side is cancelled from the solution anddP₊ is calculated as:

dP ₊=1/2dP

and dP⁻ as,

dP ⁻=1/2dP

The apparatus and method provide for the separation of the wave pressurein the fluid at a measurement site into forward and backward pressuresusing the pressure waveform alone dispensing with the need for anymeasurement of flow velocity. This advance allows use of technicallysimplified equipment which does not need to measure fluid flow velocity.

In the apparatus and method embodying the invention, the pressuremeasurements are made at baseline during the free wave period and notduring hyperaemia. This is contrary to the teaching of FFR measurementin combined flow rate and pressure measurement apparatus wheremeasurements are specifically taken at hyperaemia. This is becauseexamples of the invention extract the forward pressure component, ratherthan (as in conventional FFR) having to minimise the contribution ofbackward pressure from the measured pressure by administration ofvasodilators. If measurements are made during vasodilator hyperaemia,then measurements will not be reliable as dU increases significantly atthis time.

FIG. 4 shows an example of dU fluctuating over a cycle. There is anidentifiable window where dU tends to zero (marked at 580 ms through to770 ms in this example). The window is identified for example by being:heuristically learnt by the processor; linked to characteristics of thepressure waveform; or a certain time window after another event in thewaveform e.g. starting at a predetermined time (250 ms) after event ofdU_(max) and lasting for a predetermined period (150 ms)—note dU_(max)can be reliably observed from pressure measurements of the waveform. Thewave free period is identifiable using online analysis in real time orcan be identified using offline analysis

For example, in a cardiac environment, detecting minimised dU (wave freeperiod) from pressure measurements can be carried out as follows:

identify peak pressure time (t_(Pmax))

identify end of pressure waveform time (t_(Pend))

sample pressure measurements from t_(Pmax) to t_(Pend)

analyse pressure measurements from (t_(Pmax)+150 ms) through to(t_(Pend) −50 ms)=wave free period.

Another example for identifying the wave free period is to base itsidentification on characteristics of the pressure waveform. This isadvantageous because identification is not tied to fixed time points. Inthis specific example: calculate the isolated forward (or backward)pressure ratio;

-   -   calculate standard deviation of isolated forward (or backward)        pressure ratio select the time period (free wave period) after        peak pressure time point where the standard deviation is in the        lowest 5% and if no points are identified, select the time        period where the standard deviation is in the lowest 10% and so        on.        The measurements are continuous within the identified free wave        period and/or for a period of at least ˜=100 ms.

Another example for identifying the free wave period is:

identify the peak pressure time point;

identify the end of the pressure waveform time point; and

specifying the free wave period as a predetermined portion mid-windowbetween these two time points. Preferably, the free wave period isidentified as the mid 3/5 window between these two time points.

In the cardiac environment, reliable measurements are taken in thewindow where dU varies less than +/−2×10⁻⁴ from the zero crossing, wheredU_(max) is 3×10⁻³, where dU is 20% or less of dU_(max), preferably 10%or less, most preferably 5% or less. dU oscillates around the mean overthe wave free period so its net contribution to separated pressures(i.e. P₊) is minimised as the −ve contributions cancel the +vecontributions. The oscillations about the mean during the wave freeperiod (the time window) in a cardiac environment are due to limitationsin the measurement equipment which will not detect small changesaccurately.

Further this advance provides a measure of the severity of aconstriction using the measure of isolated pressure ratio.

Further this advance negates the need in the cardiac environment for theadministration of potent vasodilators.

There are particular needs in the cardiac environment for simplifiedequipment having the smallest possible footprint (or being the leastinvasive requiring the smallest possible entry site) so the provision ofan isolated pressure ratio measurement device or probe which has onlyone measurement device mounted on or in the probe represents asignificant technical advance in that field.

Further, such devices or probes in the cardiac field include signallines from the probe which terminate either in a transmitter forrelaying the measurement signal to a processor or a processor itself. Ifthere is a flow sensor and a pressure sensor, then two differentmeasurement devices are in/on the same probe and there are also twosignal lines required to take the signal from the two distinctmeasurement devices. The loss, in examples of the invention, of the flowsensor from the system is extremely beneficial as it reduces thecomplexity of the device, can improve handling of the probe and canreduce the number of signal lines necessary to take the measurementsignal(s) away from the measurement devices. In the case of examples ofthe invention, there is only one measurement device—that of pressuremeasurement and the need for a flow sensor in addition to one or morepressure sensors is obviated. A single pressure sensor wire can be moremaneuverable than a wire with both pressure and flow sensors. Having aflow sensor in addition to the pressure sensor is sub-optimal for guidewire design

Pressure-only measurements are taken relative to the constriction.Multiple measurements can be taken in preference to one measurement. Theprobe 2 can be moved relative to the constriction, in which case,multiple measurements would be taken.

There is a further sophistication to the above described apparatus andmethod which concerns the identification of wave free periods—thosetimes in the cyclic flow when dU tends to zero. A person skilled in theart is able to calculate and identify wave free periods—occurring asthey do during periods of the cardiac cycle when wave activity isminimised or absent.

For a given wave free period from time point tw₀ to time point tw₁: withP₊ (during any wave free period tw₀ to tw₁) as,

P ₊=∫_(tw0) ^(tw1) dP ₊

and P⁻ as,

P ⁻=∫_(tw0) ^(tw1) dP ⁻

where P_(+proximal) is defined as,

P _(+proximal)=∫_(tw0) ^(tw1) dP _(+proximal)

and P_(+distal) is defined as,

P _(+distal)=∫_(tw0) ^(tw1) dP _(+distal)

and P_(−proximal) is defined as,

P _(−proximal)=∫_(tw0) ^(tw1) dP _(−proximal)

and P_(−distal) is defined as,

P _(−distal)=∫_(tw0) ^(tw1) dP _(−distal)

The isolated pressure ratio using separated pressures is thus isolatedforward pressure:

$\frac{P_{+ {distal}}}{P_{+ {proximal}}}$

Or isolated backward pressure,

$\frac{P_{- {distal}}}{P_{- {proximal}}}$

Calculating the isolated pressure ratio using this technique over thewave free period gives a pressure-only assessment of the severity of theconstriction, such as a stenosis. There is no need to provide flowvelocity measurement equipment on the probe 2 in addition to thepressure measurement transducer 3 and there is no need to process anyflow velocity measurement.

When used in this specification and claims, the terms “comprises” and“comprising” and variations thereof mean that the specified features,steps or integers are included. The terms are not to be interpreted toexclude the presence of other features, steps or components.

The features disclosed in the foregoing description, or the followingclaims, or the accompanying drawings, expressed in their specific formsor in terms of a means for performing the disclosed function, or amethod or process for attaining the disclosed result, as appropriate,may, separately, or in any combination of such features, be utilised forrealising the invention in diverse forms thereof.

1. A method of assessing a narrowing in a blood vessel, the methodcomprising: obtaining pressure measurements from within the blood vesselusing at least one pressure-sensing probe, the pressure measurementsbeing obtained not during hyperaemia; identifying a wave free periodcorresponding to a time window when a differential of flow velocity isminimal or absent; and calculating a pressure ratio using the pressuremeasurements obtained during the wave free period to provide anassessment of a severity of the narrowing in the blood vessel.
 2. Themethod of claim 1, wherein the wave free period is identifiedheuristically.
 3. The method of claim 1, wherein the wave free period isidentified based on a characteristic of a pressure waveform of theobtained pressure measurements.
 4. The method of claim 1, wherein thewave free period is identified as a certain time window before or aftera characteristic of the pressure waveform.
 5. The method of claim 1,wherein the wave free period is identified by: identifying a peakpressure time (t_(Pmax)); identifying an end of pressure waveform time(t_(Pend)); and specifying the wave free period as a time window betweent_(Pmax) and t_(Pend).
 6. The method of claim 5, wherein the time windowextends from t_(Pmax)+150 ms to t_(Pend)−50 ms.
 7. The method of claim5, wherein the time window is a mid 3/5 window between t_(Pmax) andt_(Pend).
 8. The method of claim 1, wherein the wave free period isidentified by: calculating a standard deviation of a pressure ratio ofthe obtained pressure measurements; and specifying the wave free periodas a time window after a peak pressure time point where the standarddeviation is below a predetermined threshold.
 9. The method of claim 8,wherein the predetermined threshold is a bottom 10% or less of thecalculated standard deviation.
 10. The method of claim 8, wherein thetime window has a length of at least 100 ms.
 11. A system of assessing anarrowing in a blood vessel, the system comprising: a processor incommunication with at least one pressure-sensing probe, the processorconfigured to: receive pressure measurements obtained by at least onepressure-sensing probe positioned within the blood vessel, the pressuremeasurements being obtained not during hyperaemia; identify a wave freeperiod corresponding to a time window when a differential of flowvelocity is minimal or absent; and calculate a pressure ratio using thepressure measurements obtained during the wave free period to provide anassessment of a severity of the narrowing in the blood vessel.
 12. Thesystem of claim 11, wherein the processor is configured to identify thewave free period heuristically.
 13. The system of claim 11, wherein theprocessor is configured to identify the wave free period based on acharacteristic of a pressure waveform of the obtained pressuremeasurements.
 14. The system of claim 11, wherein the processor isconfigured to identify the wave free period as a certain time windowbefore or after a characteristic of the pressure waveform.
 15. Thesystem of claim 11, wherein the processor is configured to identify thewave free period by: identifying a peak pressure time (t_(Pmax));identifying an end of pressure waveform time (t_(Pend)); and specifyingthe wave free period as a time window between t_(Pmax) and t_(Pend). 16.The system of claim 15, wherein the time window extends fromt_(Pmax)+150 ms to t_(Pend)−50 ms.
 17. The system of claim 15, whereinthe time window is a mid 3/5 window between t_(Pmax) and t_(Pend). 18.The system of claim 11, wherein the processor is configured to identifythe wave free period by: calculating a standard deviation of a pressureratio of the obtained pressure measurements; and specifying the wavefree period as a time window after a peak pressure time point where thestandard deviation is below a predetermined threshold.
 19. The system ofclaim 18, wherein the predetermined threshold is a bottom 10% or less ofthe calculated standard deviation.
 20. The system of claim 18, whereinthe time window has a length of at least 100 ms.